| Pinoresinol diglucoside(PDG)is a kind of lignans extracted from eucommia ulmoides,bidirectional adjustment of blood pressure has a step-up and step-down,main antihypertensive effect on blood pressure in two-way adjustment,especially in the antihypertensive effect. Pharmacological activity and mechanism of eucommia ulmoides extractive has been reported,but the pharmacokinetics and main metabolites of Pinoresinol diglucoside is in a blank.The pharmacokinetics and excretion of pinoresinol diglucoside in rats are to be investigated in this paper,furthermore the cleavage pathways of pinoresinol diglucoside and its main metabolites are to be deduced.In order to elucidate the metabolic information and kinetic disposition of pinoresinol diglucoside and to Provid a basis for its effective material base and development,we further investigated the metabolites of pinoresinol diglucoside in vitro and vivo of rats. In this thesis,a rapid,sensitive and specific ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry(UPLC-ESI/MS/MS) method was developed and validated to quantify Pinoresinol diglucoside, Pinoresinol(PIN),Enterolactone(ENL),Enterodiol(END) in rat plasma and applied pharmacokinetics study.1、The development of UPLC-MS/MS method for the determination of PDG,PIN,ENL and END in plasma samplesThe optimized chromatography and mass condition for the determination of all four drugs in rat plasma were obtained,and then a ultra-performance liquid chromatography electrospray ionization tandem mass spectrometry method was developed and fully validated. The calibration curves of all four drugs showed good linearity within the range 1-1000 ng/m L(r2>0.992) and LLOQ of this method was 1 ng/m L. The extraction recoveries of all four drugs had a good reproducibility and the intra-day and inter-day RSD,R.E was less than 15%,respectively. We have developed a rapid,simple and sensitive UPLC-ESI/MS/MS method and the method was enough to qualify its application in the pharmacokinetics study of all four drugs in rats.2、Studies on pharmacokinetics of PDG,PIN,ENL and END in ratsA rapid UPLC-ESI/MS/MS method was used to a pharmacokinetics study and the determination of all four drugs in rat plasma after a single oral administration of 20 mg/kg. The mean Cmax val ues is 638.43±43.52 ng/m L,the AUC(0-∞) values is 2354.42±832.94 ng/m L·h. The mean Tmax values is 0.089±0.02 h.The mean t1/2α values is 1.17±0.24 h.The mean t1/2β values is 4.553±2.32 h.The mean V/F values is 31.01±2.03 L/kg.The mean CL/F values is 16.69±1.09 L/h/kg.The result showed that the PDG in rats were best fitted to two-compartment model.The other three drugs not detected or trace detected.3、Excretion studies of Pinoresinol diglucoside,Pinoresinol, Enterolactone, Enterodiol in ratsThe concentration of PDG in urine was determined by means of UPLC-ESI/MS/MS method was developed to research the cumulative voiding of PDG in rat urine. The results showed that the amounts excreted in urine in the form of prototype PDG was 27.45±2.51% in 0-60 h,and in the form of metabolin PIN,END and ENL were 1.08±0.29%,2.4±0.39%' 4.20±0.49%4、Study on the metabolites of Pinoresinol diglucoside in vitro of ratsWe determined the metabolites of in rats urine after oral administration of Pinoresinol diglucoside at a dosage of 20 mg/kg by high resolution mass spectrometer of Triple TOF.As a result,13 metabolites were detected in rats urine,then the cleavage pathways of pinoresinol diglucoside are to be speculated。In this paper,we Establish a analysis method of UPLC/MS/MS,and pharmacokinetics studie and excretion studies used this method;At last,we determined the metabolites of in rats urine after oral administration of Pinoresinol diglucoside at a dosage by high resolution mass spectrometer of Triple TOF,and the cleavage pathways of pinoresinol diglucoside are to be speculated。... |
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